Arindam CHAKRABORTY, Prabha ADHİKARİ, Shalini SHENOY, Shrikala BALİGA, Satish RAO, Dhanashree BİRANTHABAİL, Vishwas SARALAYA

Ekstra intestinal Escherichia coli izolatlarından GSBL, MBL ve AmpC ? laktamazların salınımı: Tedavi ve klinik sonuçlarla uyumu

Amaç: Ekstra intestinal patojenik Escherichia coli (EİPEC) izolatlarından salınan GSBL, AmpC ? laktamazlar ve Karbapenemazların salınımını ve bu hastaların tedavisi ve klinik gidişle ilişkisini araştırdık.Yöntemler: Çalışmaya 300 EİPEC ile enfekte hasta alındı. Demografik veriler, antibiyogram, tedavisi ve sonuçları toplandı. GSBL üretimi kombine disk metodu ve AmpC üretimi AmpC-disk testi ile tespit edildi. Karbapenemaz salınımına modifiye Hodge testi ile doğrulanmış disk diffüzyonla bakıldı. Metallo-?-laktamaz (MBL) aktivitesi karbapenem-EDTA kombine disk metodu ve MBL E-test ile çalışıldı. Bulgular: Üç yüz E. coli izolatının 212'si (% 71) GSBL pozitif idi. AmpC ? laktamaz üretimi 95 (% 32) görüldü; izolatların 16'sı (% 17) saf AmpC üretirken, 79'u (% 83) GSBL ile beraberdi. Karbapenemaz üreten yirmi dokuz (% 9,5) izolatın 15'i (% 5) MBL üretiyordu. Tedavi için, en yaygın olarak reçete edilen antibiyotikler ?-laktam + ?-laktamaz inhibitör kombinasyonları (% 39) idi. Hastaların % 67'i iyileşti; nüks/yeni enfeksiyon hastaların % 18'inde görülürken % 11 hasta da öldü. Kan dolaşımı enfeksiyonu olan ve sık nüks eden idrar yolu enfeksiyonlarında mortalite daha yüksekti.Sonuç: Karbepenamazlarla birlikte GSBL veya AMPC üreten EİPEC özellikle klinisyenler için dünya çapında büyük bir tehdit oluşturmaktadır ? laktam + ? laktamaz inhibitör kombinasyonu gibi uygun antibiyotiklerin erken kullanımı muhtemelen bu hastalarda komplikasyonları azaltacaktır.

Expression of ESBL, MBL and AmpC ? lactamases by extra intestinal Escherichia coli isolates: correlation with treatment and clinical outcome

Objective: We investigated the expression of Extended Spectrum ?-Lactamases (ESBLs), AmpC ? lactamases and Carbapenemases in extraintestinal pathogenic Escherichia coli (ExPEC) isolates and correlated with treatment and outcome of the patients. Methods: Three hundred ExPEC infected patients were included in the study. Demographic data, antibiogram, treatment and outcome were collected. Production of ESBLs was detected by combination disk method; AmpC was detected by AmpC disk test. Carbapenemase production was detected by disk diffusion and confirmed by modified Hodge test. Identification of metallo- ?-lactamase (MBL) activity was performed by the carbapenem-EDTA combined disk method and MBL E-test. Results: Out of 300 E. coli isolates, 212 (71%) were ESBL producers. AmpC ? lactamase production was seen in 95 (32%) isolates; 16 (17%) isolates were pure AmpC producers whereas 79 (83%) were ESBL co-producers. Twenty nine (9.5%) isolates were carbapenemase producers of which 15 (5%) were MBL producers. For treatment, most widely prescribed antibiotics were ?-lactam+?-lactamase inhibitor combinations (39%). Sixty seven percent patients improved; relapse/re-infection was seen in 18% of patients and 11% patients expired. Increased mortality was seen in patients with blood stream infection and more number of relapses was seen in urinary tract infection.Conclusion: ExPEC producing ESBL or AmpC along with carbapenemases are particularly challenging for clinicians and are a major threat worldwide. Early use of appropriate antibiotics like ?-lactam+?-lactamase inhibitor combinations will probably reduce complications in these patients.

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1. Russo TA, Johnson JR proposal for a new inclusive designation for extraintestinal pathogenic isolates of Escherichia coli: ExPEC. J Infect Dis 2000; 181:1753-1754.
2. Getzlaff PS, Polsfuss S, Poledica M, et al. Detection of AmpC Beta- Lactamase in Escherichia coli: Comparison of Three Phenotypic Confirmation Assays and Genetic Analysis. J Clin.Microbiol 2011; 49:2924-2932.
3. Naas T, Cuzon G, Bogaerts P, Glupczynski Y, Nordmann P. Evaluation of a DNA Microarray for Rapid Detection of TEM, SHV and CTX-M Extended-Spectrum ?- Lactamases and of KPC, OXA-48, VIM, IMP and NDM-1 Carbapenemases. J ClinMicrobiol 2011;49:1608-1613.
4. Lascols C, Hackel M, Marshall HS, et al. Increasing prevalence and dissemination of NDM-1metallo ? lactamase in India: data from the SMART study (2009). J Antimicrob Chemother 2011; 66:1992-1997.
5. Sharma S, Bhat GK, Shenoy S. Virulence Factors and Drug Resistance in Escherichia coli isolated from extraintestinal infection. Indian J Med Microbiol 2007; 25:369-373.
6. Clinical and laboratory standards institute.2010. Performance standards for antimicrobial susceptibility testing. CLSI M100- S20U. Update June 2010. Clinical and Laboratory Standards Institute, Wayne, PA, USA.
7. Black JA, Moland ES, Thomson KS. AmpC disk test for detection of plasmid - mediated AmpC ? lactamases in Enterobacteriaceae lacking chromosomal AmpC ? lactamases. J Clin Microbiol 2005; 43:3110-3113.
8. Yan JJ, Wu JJ, Tsai SH Chuang CL. Comparison of the double-disk, combined disk and E-test methods for detecting metallo-?-lactamases in gram- negative bacilli. Diagn Microbiol Infect Dis 2004; 49:5-11.
9. Yong D, Toleman AM, Giske GC, et al. Characterization of a new Metallo- ?- lactamase gene, blaNDM-1, and a novel Erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009; 53:5046-5054.
10. Goyal A, Prasad KN, Prasad A, Gupta S, Ghoshal U, Ayyagari A. Extended spectrum ?-lactamases in Escherichia coli & Klebsiella pneumoniae& associated risk factors Indian J Med Res 2009; 129:695-700.
11. Luvsansharav O.U, Hirai I, Niki M, et al. Analysis of risk factors for a high prevalence of extended- spectrum ? lactamase- producing Enterobacteriaceae in asymptomatic individuals in rural Thailand. J Med Microbiol 2011; 60:619-624.
12. Chandel SD, Johnson AJ, Chaudhry R, et.al. Extended spectrum ? lactamase producing Gram-negative bacteria causing neonatal sepsis in India in rural and urban settings. J Med Microbiol 2011;60.500-507.
13. Khalifa SG, Einass E, Nuri B. Uropathogens from diabetic patients in Libya: virulence factors and phylogenetic groups of Escherichia coli isolates. J Med Microbiol 2009; 58:1006- 1014. 14. Hamalatha V, Padma M, Sekar U, Vinod TM, Arunkumar AS. Detection of AmpC ? Lactamases production in Escherichia coli and klebsiella sp by an inhibitor based method. Indian J Med Res 2007; 126:220-223.
15. Sinha P, Sharma R, Rishi S, Sood S, Pathak D. Prevalence of extended spectrum ? lactamase and AmpC ?- lactamase producers among Escherichia coli isolates in a tertiary care hospital in Jaipur. Ind J Pathol Microbiol 2008; 51:367-369.
16. Mulvey RM, Bryce E, Boyd AD, et al. Molecular characterization of cefoxitin resistance Escherichia coli from Canadian hospitals. Antimicrob Agents Chemother 2005; 49;358-365.
17. Munier GK, Johnson CL, Snyder JW, Moland ES, Hanson ND, Thomson KS. Positive extended-spectrum-beta-lactamase (ESBL) screening results may be due to AmpC beta-lactamases more often than to ESBLs. J Clin Microbiol 2010;48:673-677.
18. Bell JM ,Chitsaz M, Turnidge DJ, Barton M, Walters JL, Jones NR. Prevalence and significance of a negative extended-spectrum ?-lactamase (ESBL) confirmation test result after a positive ESBL screening test result for isolates of Escherichia coli and Klebsiella pneumoniae: results from the SENTRY Asia-Pacific surveillance program. J Clin Microbiol 2007;45:1478-1482.
19. Getzlaff PS, Polsfuss S, Poledica M, et.al. Detection of AmpC ? lactamase in Escherichia coli: Comparison of three phenotypic confirmation assays and genetic analysis. J Clin Microbiol 2011; 49: 2924-2932.
20. Mohanty S, Gaind R, Deb M. Prevalence and phenotypic characterization of carbapenem resistance in Enterobacteriaceae blood stream isolates in a tertiary care hospital in India. Int J Antimicrob Agents 2011;37:270-281.
21. Gupta E, Mohanty S, SoodS, Dhawan B, Das KB, Kapil A. Emerging resistance to carbapenems in a tertiary care hospital in north India. Indian J Med Res 2006;124:95-98.
22. Karabinis A, Paramythiotou E, Petropoulou MD, et al. Colistin for Klebsiella pneumoniae associated sepsis. Clin Infect Dis 2004;38: E7-E9.
23. Linden PK, Kusne S, Coley K, Fontes P, Kramer JD, Peterson D. Use of parenteral colistin for the treatment of serious infection due to antimicrobial resistance Pseudomonas aeruginosa. Clin Infect Dis 2003;37:E154-E160.
24. Jaureguy .F, Carbonnelle E, Bonacorsi S, et al. Host and bacterial determinants of initial severity and outcome of Escherichia coli sepsis. Clin MicrobiolInfect 2007;13:854-862.
25. Igra SY, Fourer B, Wasserlauf RO, et al. Reappraisal of community acquired bacteremia: A proposal of a new classification for the spectrum of acq